Resistance Exercise and Supraphysiologic Androgen Therapy in Eugonadal Men With HIV-Related Weight Loss: A Randomized Controlled Trial | Endocrinology | JAMA | JAMA Network
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Kotler DP, Tierney A, Wang J.  et al.  Magnitude of body cell mass depletion and timing of death from wasting in AIDS.  Am J Clin Nutr.1989;50:444-447.Google Scholar
Suttman U, Ockenga J, Selberg O, Hoogestraat L, Deicher H, Muller MJ. Incidence and prognostic value of malnutrition and wasting in human immunodeficiency virus-infected out-patients.  J AIDS Hum Retrovirol.1995;8:239-246.Google Scholar
Kotler DP, Tierney A, Culpepper-Morgan J.  et al.  Effect of home total parenteral nutrition on body composition in patients with acquired immunodeficiency syndrome.  JPEN J Parenter Enteral Nutr.1990;14:454-458.Google Scholar
Hoh R, Pelfini A, Neese RA.  et al.  De novo lipogenesis predicts short-term body composition response by bioelectrical impedance analysis to oral nutritional supplements in HIV-associated wasting.  Am J Clin Nutr.1998;68:154-163.Google Scholar
Von Roenn JH, Armstrong D, Kotler DP.  et al.  Megestrol acetate in patients with AIDS related cachexia.  Ann Intern Med.1994;121:393-399.Google Scholar
Oster MH, Enders SH, Samuels ST.  et al.  Megestrol acetate in patients with AIDS and cachexia.  Ann Intern Med.1994;121:400-408.Google Scholar
Carr A, Samaras K, Burton S.  et al.  A syndrome of peripheral lipodystrophy, hyperlipidemia and insulin resistance due to HIV protease inhibitors. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 2-5, 1998; Chicago, Ill. Abstract 410:156.
Hengel RL, Geary JAM, Vuchetich MA.  et al.  Multiple symmetrical lipomatosis associated with protease inhibitor therapy. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections; February 2-5, 1998; Chicago, Ill. Abstract 407:156.
Roth VR, Angel JB, Kravcik S.  et al.  Development of cervical fat pad following treatment with HIV-1 protease. In: Program and abstracts of the 5th Conference on Retroviruses and Opportunistic Infections, February 2-5, 1998, Chicago, Ill. Abstract 411:157.
Silva M, Skolnick P, Gorbach S.  et al.  Effects of protease inhibitors on weight and body composition in HIV-infected patients.  AIDS.In press.Google Scholar
Dobs AS, Dempsey MA, Landenson PW.  et al.  Endocrine disorders in men infected with HIV.  Am J Med.1988;84:611-616.Google Scholar
Hellerstein MK, Grunfeld C, Wu K.  et al.  Increased de novo hepatic lipogenesis in human immunodeficiency virus infection.  J Clin Endocrinol Metab.1993;76:559-565.Google Scholar
Mulligan K, Grunfeld C, Hellerstein MK.  et al.  Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection.  J Clin Endocrinol Metab.1993;77:956-962.Google Scholar
Schambelan M, Mulligan K, Grunfeld C.  et al.  Recombinant human growth hormone in patients with HIV-associated wasting.  Ann Intern Med.1996;125:873-882.Google Scholar
Strawford A, Van Loan M, King J, Hellerstein M. Effects of nandrolone decanoate on nitrogen balance, lean body mass, metabolic abnormalities and performance in borderline hypogonadal men with HIV-associated weight loss.  J AIDS Hum Retrovirol.1998;20:137-147.Google Scholar
Grinspoon S, Corcoran C, Askari H.  et al.  Effects of androgen administration in men with the AIDS wasting syndrome: a randomized, double-blind, placebo-controlled trial.  Ann Intern Med.1998;129:18-26.Google Scholar
Hellerstein MK. Nutritional and endocrine consequences of HIV infection. In: Crowe S, Hoy J, Mills J, eds. Management of the HIV-Infected Patient. New York, NY: Cambridge University Press; 1996:194-205.
Bhasin S, Storer TW, Berman N.  et al.  The effects of supraphysiologic doses of testosterone on muscle size and strength in normal men.  N Engl J Med.1996;335:1-7.Google Scholar
Mendenhall CL, Moritz TE, Roselle GA.  et al.  A study of oral nutritional support with oxandrolone in malnourished patients with alcoholic hepatitis.  Hepatology.1993;17:564-576.Google Scholar
Mendenhall CL, Anderson S, Garcia-Pont P.  et al.  Short-term and long-term survival in patients with alcoholic hepatitis treated with oxandrolone and prednisolone.  N Engl J Med.1984;311:1464-1470.Google Scholar
Malhotra A, Poon E, Tse WY, Pringle PJ, Hindmarsh PC, Brook CG. The effects of oxandrolone on the growth hormone and gonadal axis in boys with constitutional delay of growth and puberty.  Clin Endocrinol.1993;38:393-398.Google Scholar
World Health Organization.  Energy and Protein Requirements: Report of a Joint FAO/WHO/UNU Expert ConsultationGeneva, Switzerland: World Health Organization; 1985. Technical Report Service 724; 206.
Kraemer WJ, Fry AC. Strength testing: development and evaluation of methodology. In: Maud PJ, Foster C, eds. Physiological Assessment of Human Fitness: Human Kinetics. Champaign, Ill: Human Kinetics; 1995:115-137.
Berner DL, Brown J. Protein nitrogen combustion method collaborative study 1: comparison of total Kjeldahl nitrogen and combustion results.  J Am Oil Chem Soc.1994;71:1291-1293.Google Scholar
Cook JGH. Factors influencing the assay of creatinine.  Ann Clin Biochem.1975;12:219.Google Scholar
Hellerstein MK, Christiansen M, Kaempfer S.  et al.  Measurement of de novo hepatic lipogenesis in humans using stable isotopes.  J Clin Invest.1991;87:1841-1852.Google Scholar
Hellerstein MK, Neese R. Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers.  Am J Physiol.1992;263(5 pt 1):E988-E1001.Google Scholar
Hellerstein MK, Schwarz JM, Neese RA. Regulation of hepatic de novo lipogenesis in humans.  Annu Rev Nutr.1996;16:523-557.Google Scholar
Catlin DH, Kammerer RC, Hatton CK.  et al.  Analytical chemistry at the games of the XXIIIrd Olympiad in Los Angeles.  Clin Chem.1987;33:319-327.Google Scholar
Catlin DH, Hatton CK, Starcevic SH. Issues in detecting abuse of anabolic steroids and testosterone by analysis of athletes' urine.  Clin Chem.1997;43:1280-1288.Google Scholar
Forbes GB. Human Body Composition; Growth, Aging, Nutrition and ActivityNew York, NY: Springer-Verlag NY Inc; 1987:64-71.
Catlin DH. Anabolic steroids. In: DeGroot L, ed. Endocrinology. 3rd ed. Orlando, Fla: WB Saunders; 1995:2362-2376.
Klein S, Kinney J, Jeejeebhoy K.  et al.  Nutrition support in clinical practice: review of published data and recommendations for future research directions, summary of Expert Conference Sponsored by the National Institutes of Health, American Society for Parenteral and Enteral Nutrition, and American Society for Clinical Nutrition.  Am J Clin Nutr.1997;66:683-706.Google Scholar
Fujioka M, Shinohara Y, Baba S.  et al.  Pharmacokinetic properties of testosterone propionate in normal men.  J Clin Endocrinol Metab.1986;63:1361-1364.Google Scholar
Nindl B, Friedl K, Frykman P.  et al.  Physiologic recovery after severe weight loss [abstract].  FASEB J.1994;8:A724.Google Scholar
Fruth SJ, Worrell TW. Factors associated with menstrual irregularities and decreased bone mineral density in female athletes.  J Orthop Sports Phys Ther.1995;22:26-38.Google Scholar
Tvede N, Kaplan G, Halkjaer-Kristensen J.  et al.  The effect of light, moderate and severe bicycle exercise on lymphocyte subsets, natural and lymphokine activated killer cells, lymphocyte proliferative response and interleukin-2 production.  Int J Sports Med.1993;14:275-282.Google Scholar
Cannon JG, Fielding RA, Fiatarone MA.  et al.  Increased interleukin 1b in human skeletal muscle after exercise.  Am J Physiol.1989;257 (2 pt 2):R451-R455.Google Scholar
Evans WJ, Cannon JG. The metabolic effects of exercise-induced muscle damage.  Exerc Sport Sci Rev.1991;19:99-125.Google Scholar
Appelbaum DM, Haffner S, Hazzard WR. The dyslipoproteinemia of anabolic steroid therapy: increase in hepatic triglyceride lipase precedes the decrease in high density lipoprotein-2 cholesterol.  Metabolism.1987;36:945-952.Google Scholar
Grunfeld C, Kotler DP, Hamadeh R, Tierney A, Wang J, Pierson R. Hypertriglyceridemia in the acquired immunodeficiency syndrome.  Am J Med.1989;86:27-31.Google Scholar
Wheeler DA, Muurahainen N, Launer C, Gilbert C, Bartsch G. Change in body weight (wt) as a predictor of death and opportunistic (OC) in HIV by history of prior OC. In: Program and abstracts of the 11th International Conference on AIDS; July 7-12, 1996; Vancouver, British Columbia. Abstract Tu.B 2383:332.
Original Contribution
April 14, 1999

Resistance Exercise and Supraphysiologic Androgen Therapy in Eugonadal Men With HIV-Related Weight Loss: A Randomized Controlled Trial

Author Affiliations

Author Affiliations: Department of Nutritional Sciences, University of California, Berkeley (Drs Strawford, Parks, Neese, Christiansen, and Hellerstein); Division of Endocrinology and Metabolism, Department of Medicine, San Francisco General Hospital, University of California, San Francisco (Drs Hellerstein and Christiansen); Western Human Nutrition Research Center, United States Department of Agriculture, Presidio of San Francisco (Ms Barbieri and Drs Van Loan and King); Human Nutrition Unit, London School of Hygiene and Tropical Medicine, London, England (Dr Strawford); Biotechnology General Corporation, Iselin, NJ (Dr Barton); and Department of Molecular and Medical Pharmacology, University of California, Los Angeles (Dr Catlin).

JAMA. 1999;281(14):1282-1290. doi:10.1001/jama.281.14.1282

Context Repletion of lean body mass (LBM) that patients lose in human immunodeficiency virus (HIV) infection has proved difficult. In healthy, HIV-seronegative men, synergy between progressive resistance exercise (PRE) and very high-dose testosterone therapy has been reported for gains in LBM and muscle strength.

Objective To determine whether a moderately supraphysiologic androgen regimen, including an anabolic steroid, would improve LBM and strength gains of PRE in HIV-infected men with prior weight loss and whether protease inhibitor antiretroviral therapy prevents lean tissue anabolism.

Design Double-blind, randomized, placebo-controlled trial; post hoc analysis for effect of HIV-protease inhibitor therapy conducted from January to October 1997.

Setting Referral center in San Francisco, Calif.

Patients Volunteer sample of 24 eugonadal men with HIV-associated weight loss (mean, 9% body weight loss), recruited from an AIDS clinic and by referral and by advertisement.

Intervention For 8 weeks, all subjects received supervised PRE with physiologic intramuscular testosterone replacement (100 mg/wk) to suppress endogenous testosterone production. Randomization was between an anabolic steroid, oxandrolone, 20 mg/d, and placebo.

Main Outcome Measures Lean body mass, nitrogen balance (10-day metabolic ward measurements), body weight, muscle strength, and androgen status.

Results Twenty-two subjects completed the study (11 per group). Both groups showed significant nitrogen retention and increases in LBM, weight, and strength. The mean (SD) gains were significantly greater in the oxandrolone group than in the placebo group (5.6 [2.1] vs 3.8 [1.8] g of nitrogen per day [P=.05]; 6.9 [1.7] vs 3.8 [2.9] kg of LBM [P=.005];greater strength gains for various upper and lower body muscle groups by maximum weight lifted [P=.02-.05] and dynamometry [P=.01-.05]). The mean (SD) high-density lipoprotein cholesterol level declined 0.25 (0.14) mmol/L (9.8 [5.4] mg/dL) significantly in the oxandrolone group (P<.001 compared with placebo). Results were similar whether or not patients were taking protease inhibitors. One subject in the oxandrolone group discontinued the study because of elevated liver function test results.

Conclusions A moderately supraphysiologic androgen regimen that included an anabolic steroid, oxandrolone, substantially increased the lean tissue accrual and strength gains from PRE, compared with physiologic testosterone replacement alone, in eugonadal men with HIV-associated weight loss. Protease inhibitors did not prevent lean tissue anabolism.